title: Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs.
abstract: Structural remodeling in chronic atrial fibrillation (AF) occurs over weeks to months. To study the electrophysiological, structural, and functional changes that occur in chronic AF, the selection of the best animal model is critical. AF was induced by rapid atrial pacing (50-Hz stimulation every other second) in pigs (n = 4), dogs (n = 8), and goats (n = 9). Animals underwent MRIs at baseline and 6 mo to evaluate left ventricular (LV) ejection fraction (EF). Dogs were given metoprolol (50-100 mg po bid) and digoxin (0.0625-0.125 mg po bid) to limit the ventricular response rate to <180 beats/min and to mitigate the effects of heart failure. The pacing leads in pigs became entirely encapsulated and lost the ability to excite the heart, often before the onset of sustained AF. LV EF in dogs dropped from 54 ± 11% at baseline to 33 ± 7% at 6 mo (P < 0.05), whereas LV EF in goats did not drop significantly (69 ± 8% at baseline vs. 60 ± 9% at 6 mo, P = not significant). After 6 mo of AF, fibrosis levels in dog atria and ventricles increased, whereas only atrial fibrosis levels increased in goats compared with control animals. In our experience, the pig model is not appropriate for chronic rapid atrial pacing-induced AF studies. Rate-controlled chronic AF in the dog model developed HF and LV fibrosis, whereas the goat model developed only atrial fibrosis without ventricular dysfunction and fibrosis. Both the dog and goat models are representative of segments of the patient population with chronic AF.
authors.affiliation: Comprehensive Arrhythmia Research and Management Center, University of Utah, Salt Lake City, Utah; and.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Dosdall
authors.forename: Ravi
authors.initials: R
authors.lastname: Ranjan
authors.forename: Koji
authors.initials: K
authors.lastname: Higuchi
authors.forename: Eugene
authors.initials: E
authors.lastname: Kholmovski
authors.forename: Nathan
authors.initials: N
authors.lastname: Angel
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Rob
authors.initials: R
authors.lastname: Macleod
authors.forename: Layne
authors.initials: L
authors.lastname: Norlund
authors.forename: Aaron
authors.initials: A
authors.lastname: Olsen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Davies
authors.forename: Nassir F
authors.initials: NF
authors.lastname: Marrouche
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000150:complications* / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs / Q000502:physiology*; D004558:Electric Stimulation; D006041:Goats / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D013552:Swine / Q000502:physiology*; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
keywords: animal models; chronic atrial fibrillation; fibrosis; heart failure; rapid atrial pacing